1. Technical Field
The present invention relates to a composition comprising crude extract or non-polar solvent soluble extract of Dioscorea opposita having neuron-protective activity for preventing and treating brain disease.
2. Background Art
In the twentieth century, as the average life span of human has been increasing with the rapid development of life science and medicine, new social problems including increased population ratio of older people are coming to the front, especially, the chronic degenerative disease have been more rapidly increased than acute infectious diseased having been main aetiology of death for 50 years.
Among the chronic degenerative disease, a cerebrovascular disease to cause to death has become an important disease and ranked to the second frequent disease in lethal diseases to die due to single aetiology
Cerebrovascular disease can be classified into two types. One is hemorrhagic brain disease mainly occurred by external impact such as traffic accident resulting in cerebral hemorrhage and another is ischemic brain disease mainly occurred by aging and other factors resulting in cerebrovascular occlusion.
In case that temporary ischemia is occurred, the supply of oxygen and glucose are blocked to cause the decrease of ATP and edema and finally those serial phenomena give rise to extensive brain damage. The death of neuronal cells appears at considerable times after the ischemia, which is called as delayed neuronal death. Through transient forebrain ischemic model experiment using by Mongolian gerbil, it is reported that there occurred the death of neuronal cell at CA1 region of hippocampus four days after the ischemia inducement (Kirino T. Sano K., Acta Neuropathol., 62, pp 201-208, 1984; Kirino T. Brain Research, 239, pp 57-69, 1982).
There have been reported that the mechanism of neuronal cell death is classified into two types: one is excitational neuronal cell death mechanism characterized that excess amount of glutamate is accumulated in outer cell after cerebral ischemia occurred and the glutamate is flowed into inner cell apoptosis to cause to neuronal cell death due to excess accumulation of calcium ion in inner cell (Kang T. C., et al., J. Neurocytol., 30, pp 945-955, 2001); another is Oxidative neuronal cell death characterized that abrupt oxygen supply causes to the increase of in vivo radical resulting in damages of cytoplasm (Won M. H., et al., Brain Research, 836, pp 70-78, 1999; Sun A. Y., Chen Y. M., J. Biomed. Sci., 5, pp 401-414, 1998; Flowers F, Zimmerman J. J. New Horiz., 6, pp 169-180, 1998)
There have been studied and developed to search effective substance effectively inhibiting neuronal cell death and the action mechanism of the substance till now, however, there has not yet reported the substance to inhibit neuronal cell death effectively. There have been several attempts to find effective agent till now. For example, t-PA (tissue Plasminogen activator), sole FDA approved treating agent for ischemia, has thrombolytic activity which can dissolve blood thrombus to induce rapid supply of oxygen and glucose. However, it has several disadvantages such as necessity to instant use, the occurrence of hemorrhagic cerebrovascular disease caused by thinned blood vessel wall in case of excessive or frequent use of the agent. MK-801, a calcium channel blocker inhibit initial calcium influx effectively, however, the further development was postponed because of its adverse effect.
Dioscorea opposita Thunb(=Dioscorea batatas Decne.) belonged to Dioscoreacea, is originally grown in China. It is also distributed or cultivated in Korea and Japan. The rhizome of Dioscorea opposita has been used to an edible and traditional medicinal plant in Korea. It has been reported that D. opposita containing allantoin, diosgenin, dioscine, dopamine, ergosterol and so on (Nie G. H, et al; Chinese Traditional Herbal Drugs, 24, pp 158-160, 1993; Zhao G. H, et al; Acta Pharmaceutica Sinica, 38, pp 37-41, 2003) and used for treating of anorexia, chronic diarrhea, asthma, dry coughs, oligunia, diabetes and so on. However, there has been not reported or disclosed about therapeutic effect for brain disease of Dioscorea opposita in any of above cited literatures, the disclosures of which are incorporated herein by reference.
Accordingly, the present inventors have discovered that the extract of Dioscorea opposita shows neuronal cell-protective activity by inhibiting neuronal cell death and have finally completed the present invention.
These and other objects of the present invention will become apparent from the detailed disclosure of the present invention provided hereinafter.